One of the earliest, if not the primary, responses of cultured normal animal cells to treatment with polycyclic hydrocarbons (PH) is the induced synthesis of aryl hydrocarbon hydroxylase (AHH). AHH is a multicomponent membrane-bound monooxygenase which requires NADPH and molecular oxygen for the metabolism of certain exogenous substrates such as carcinogenic PH. The induction of AHH in mouse cells IN VITRO and IN VIVO, and in cultured human lymphocytes appear to be genetically controlled. Based on AHH activity in lymphocyte cultures, human subjects fall into three inducible groups (low, intermediate, high), and healthy persons with high AHH inducibility may have a greater propensity for developing lung cancer; 30% of patients with bronchogenic carcinoma falls into the high group, while only about 9% of healthy subjects fall into the high group. Thus, responsiveness of human lymphocytes to AHH induction appears to be related to a genetic variability in the occurrence of lung cancer. A relationship between lymphocyte AHH activity and other types which might arise from respiratory epithelium has not been shown. To test this hypothesis, we will determine whether cultured lymphocytes derived from adult patients with demonstrated carcinoma of the head and neck region have statistically higher levels of AHH than lymphocytes from healthy controls. This type of malignancy was chosen for the proposed study because of its cellular origin, which in some cases is respiratory epithelium; it is one of the first tissues exposed to inhaled or ingested environmental carcinogenic chemicals; and because this tumor is usually detected as primary. The immediate objectives of the proposed study are: (1) To measure the induced AHH activity in cultured lymphocytes from the peripheral blood of adult patients with head and neck cancer, and from healthy control subjects; (2) To determine the rates of proliferation of the above lymphocyte cultures systems; (3) To isolate and identify the T and B lymphocytes from healthy and cancer subjects, and compare the AHH activity in both cell populations. The long range goal of this study is to develop a reproducible cell culture system to determine man's potential susceptibility to toxic and carcinogenic environmental chemicals.